ABSTRACT Whether female germline stem cells (fGSCs) exist in postnatal mammalian ovaries has been debated for decades. Since the fGSCs were first reported in 2004, a large number of studies have been conducted using different approaches. However, the persistent controversy surrounding the results has caused confusion among many researchers and clinicians. To clearly clarify this question, we developed advanced tracing system to label any possible fGSCs in adult female mice. Our results showed that no Stra8‐expressing germ cells were detected in the ovaries of adult female mice using a long‐term uninterrupted lineage tracing system under both physiological and pathological conditions. Furthermore, we adopted the interleaved reporter tracing system that allows mutually exclusive labelling of germ cells and non‐germ cell populations while preventing potential secondary recombination. This approach revealed no evidence of de novo germ cell formation during postnatal life. Together, our findings provide the evidence that fGSCs and postnatal oogenesis do not exist under both physiological and pathological conditions in mouse models, therefore reinforcing the notion that the primordial follicle pool established perinatally serves as the primary source of oocytes through the entire reproductive lifespan.
ABSTRACT MD‐1 plays significant roles in various pathological processes closely associated with cardiovascular diseases through its functions in different cell types. However, the critical effects and molecular mechanisms mediated by MD‐1 in macrophages involved in the development of atherosclerosis remain elusive. In this study, we observed that the expression of MD‐1 was upregulated in atherosclerotic plaques derived from human carotid arteries, as analysed through the Gene Expression Omnibus database. Additionally, MD‐1 expression was elevated in the aortas of hyperlipidemic ApoE‐deficient mice and in oxidised low‐density lipoprotein‐stimulated bone marrow‐derived macrophages, as demonstrated by RT‐PCR and western blot analyses. Furthermore, MD‐1 expression exhibited strong co‐localisation with macrophages, as confirmed by double immunofluorescence staining. Notably, MD‐1 −/− ApoE −/− mice subjected to a high‐fat diet displayed a significant reduction in atherosclerotic plaques throughout the entire aorta, aortic root, and brachiocephalic arteries. Moreover, the plaques in MD‐1 −/− ApoE −/− mice were more stable, characterised by a decreased necrotic core size, reduced macrophage infiltration, and lower lipid deposition, alongside an increased accumulation of collagen and smooth muscle cells. Bone marrow transplantation from MD‐1 −/− ApoE −/− mice to ApoE −/− mice markedly attenuated the development of atherosclerosis. This attenuation was associated with an enhanced anti‐inflammatory macrophage phenotype and a reduction in pro‐inflammatory macrophage polarisation. Similar effects of MD‐1 ablation on macrophage behaviour were also observed in vitro. Mechanistically, MD‐1 deficiency inhibited the cyclic GMP‐AMP synthase‐stimulator of interferon genes‐TANK‐binding kinase 1‐IRF3 pathway, thereby attenuating NLRP3 inflammasome activation in macrophages. However, the use of the STING agonist DMXAA counteracted the effects of MD‐1 deficiency on macrophage polarisation. Our findings reveal MD‐1 promotes pro‐inflammatory (M1‐like) macrophage polarisation in atherosclerosis by inhibiting NLRP3 inflammasome activation via a cGAS‐STING dependent pathway. These results suggest that MD‐1 neutralisation could be a potential therapeutic strategy for atherosclerosis management.
ABSTRACT CRISPR–Cas9‐mediated precise gene knock‐in relies on homology‐directed repair (HDR) at low frequencies in most mammalian cells, limiting precise gene editing in both research and therapeutic applications. Although multiple strategies have been developed to increase knock‐in efficiency, their application can be restricted by technical complexity, limited applicability, or potential safety concerns. In this review, we propose a shift in focus from conventional strategies toward epigenetic methods to increase knock‐in efficiency. It has been proved that histone modifications such as H3K36me3, H3K9me3, H4K20me2, and H2AK15ub are involved in DNA damage signallings and the recruitment of key HDR and non‐homologous end joining (NHEJ) factors. We further discuss conceptual strategies for transient chromatin modulation to bias repair pathway choice and highlight associated technical challenges and safety considerations. Together, these findings and insights highlight the essential role of histone modification in shaping chromatin states and orchestrating DNA repair dynamics. Accordingly, epigenetic regulation emerges as a compelling strategy to facilitate high‐fidelity gene knock‐in, offering valuable mechanistic clues and actionable epigenetic targets to gene editing for basic research and therapeutic translation.
ABSTRACT Bioadhesives have traditionally been viewed as materials for wound closure, sealing and haemostasis However, in tissue repair they also create the first engineered interface that influences cell retention, microenvironmental homeostasis and subsequent remodelling Recent advances in 3D printing are shifting bioadhesives from passive, uniform layers to architecturally controlled interfaces with spatially programmable chemistry, mechanics, transport and biological function. In this Review, we propose an interface‐centred framework in which qualifying 3D‐printed bioadhesive interfaces function as proliferative niches. Such interfaces require stable host‐tissue adhesion and a biocompatible, cell‐permissive microenvironment. They should also measurably support cell survival, context‐appropriate proliferation and constructive remodelling in defined target‐cell populations. We summarize the key design principles that govern proliferative‐niche formation, with printability‐aware fabrication treated as a cross‐cutting prerequisite for implementing interfacial adhesion, mechanical matching, mass transport, surface chemistry and temporal evolution. We then discuss the mechanistic basis through which printed bioadhesive interfaces regulate early protein adsorption, immune activation, mechanotransduction, metabolic exchange and long‐term remodelling trajectories. Representative application contexts, including sealing and haemostasis musculoskeletal repair, wearable and implantable biointerfaces and organoid‐related in vitro models, are examined to highlight application‐specific opportunities and trade‐offs. We further outline emerging evaluation and modelling frameworks that move beyond adhesion strength towards multidimensional assessment, cross‐scale structure–property–function mapping and data‐driven predictive design. By reframing bioadhesives as active interfacial regulators rather than passive fixation materials, this Review provides a conceptual framework for engineering 3D‐printed bioadhesives that not only adhere and seal, but also actively guide constructive tissue repair.
ABSTRACT Ferroptosis, a regulated form of cell death driven by iron‐dependent lipid peroxidation, emerged as a critical process in the pathogenesis of various diseases, including neurological, cardiovascular, hepatic, pulmonary, and renal disorders. Simultaneously, N6‐methyladenosine (m 6 A), the most abundant reversible RNA modification in eukaryotes, plays a pivotal role in gene regulation by modulating RNA stability, translation, and degradation. Evidence increasingly links m 6 A modifications to the transcriptional and post‐transcriptional regulation of ferroptosis, highlighting their importance in disease mechanisms. This review explores the molecular mechanisms underpinning m 6 A modifications and ferroptosis, detailing their interactions in disease progression. Additionally, it evaluates the therapeutic promise of targeting m 6 A regulators to modulate ferroptosis, offering novel approaches for managing diseases with diverse etiologies. By clarifying the role of m 6 A in ferroptosis, this review underscores the promise of m 6 A‐focused therapeutic strategies in advancing treatment for diseases where ferroptosis plays a key pathological role.
